Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

HPV Can Damage Genes and Chromosomes Directly, Sequencing Study Shows

Published: Tuesday, November 12, 2013
Last Updated: Tuesday, November 12, 2013
Bookmark and Share
This study shows that HPV can damage genes and chromosomes directly, revealing a new way by which HPV might contribute to cancer development.

The virus that causes cervical, head and neck, anal and other cancers can damage chromosomes and genes where it inserts its DNA into human DNA, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

It’s long been known that cancer-causing types of human papillomavirus (HPV) produce two viral proteins, called E6 and E7, which are essential for the development of cancer. However, they are not sufficient to cause cancer. Additional alterations in host-cell genes are necessary for cancer to develop. Here, scientists identified a new mechanism by which HPV may damage host DNA directly and contribute to cancer development.

Published in the journal Genome Research, this laboratory study used whole-genome sequencing to investigate the relationship between the HPV and host genomes in human cancers.

“Our sequencing data showed in vivid detail that HPV can damage host-cell genes and chromosomes at sites of viral insertion,” says co-senior author David Symer, MD, PhD, assistant professor of molecular virology, immunology and medical genetics at the OSUCCC – James.

“HPV can act like a tornado hitting the genome, disrupting and rearranging nearby host-cell genes,” Symer explains. “This can lead to overexpression of cancer-causing genes in some cases, or it can disrupt protective tumor-suppressor genes in others. Both kinds of damage likely promote the development of cancer.”

“We observed fragments of the host-cell genome to be removed, rearranged or increased in number at sites of HPV insertion into the genome,” says co-senior author Maura Gillison, MD, PhD, professor of medicine, epidemiology and otolaryngology and the Jeg Coughlin Chair of Cancer Research at the OSUCCC – James. “These remarkable changes in host genes were accompanied by increases in the number of HPV copies in the host cell, thereby also increasing the expression of viral E6 and E7, the cancer-promoting genes.”

HPV causes about 610,000 cancers annually worldwide, including virtually all cervical cancers, and many anogenital and head and neck cancers. How it causes cancer isn’t completely understood.

The two cancer-causing proteins, E6 and E7, silence two key tumor-suppressor genes in host cells, contributing to cancer development. “E6 and E7 are critically important for the virus to cause cancer. Our findings shed light on how HPV, and perhaps other viruses, can disrupt the structure of host chromosomes and genes and thereby contribute to cancer development,” Gillison explains.

For this study, Symer, Gillison and their colleagues examined 10 cancer-cell lines and two head and neck tumor samples from patients. Along with whole-genome sequencing, the scientists used several molecular assays, including RNA sequencing, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH).

Key technical findings included:
•    The genome-wide analysis, at single nucleotide resolution, identified a striking and recurrent association between HPV integrants and adjacent genomic amplifications, deletions and translocations;
•    The HPV integrants mapped broadly across the human genome, with no evidence of recurrent integration into particular chromosomal hotspots;
•    The researchers proposed a “looping” model by which abnormal viral replication results in the extraordinary damage that occurs to host chromosomes at the sites of viral DNA insertion.

“Our study reveals new and interesting information about what happens to HPV in the ‘end game’ in cancers,” Symer says. “Overall, our results shed new light on the potentially critical, catastrophic steps in the progression from initial viral infection to development of an HPV-associated cancer.”

Funding from the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, the Ohio Supercomputer Center, an Ohio Cancer Research Associate grant, the Oral Cancer Foundation and the Intramural Research Program of the National Institutes of Health, National Cancer Institute Center for Cancer Research, supported this research.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More Than 4,400+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Drug May Prevent Life-Threatening Muscle Loss in Advanced Cancers
New data describes how an experimental drug can stop life-threatening muscle wasting (cachexia) associated with advanced cancers and restore muscle health.
Wednesday, November 25, 2015
How the Human Immune System Keeps TB at Bay
Scientists create model of host, bacteria behavior in latent TB infection.
Tuesday, March 31, 2015
New Genetic Discovery Could Reduce the Guesswork in Drug Dosing
Findings likely to improve how patients are prescribed one in four clinically used drugs.
Friday, October 04, 2013
Loss of MicroRNA Decoy Might Contribute to Development of Soft-Tissue Sarcoma
Knowledge of this mechanism could guide the design of new, more effective treatments.
Thursday, August 08, 2013
Nano Drug Crosses Blood-Brain Tumor Barrier
This laboratory study shows that a nanotechnology drug called SapC-DOPS crosses barrier and targets brain-tumor cells and retards growth of tumor blood vessels.
Monday, July 22, 2013
Study Shows How the Nanog Protein Promotes Growth of Head and Neck Cancer
A protein called Nanog helps the renewal of healthy embryonic stem cells and promotes cancer stem cell proliferation in head and neck cancer.
Monday, June 24, 2013
Scientific News
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Apricot Kernels Pose Risk of Cyanide Poisoning
Eating more than three small raw apricot kernels, or less than half of one large kernel, in a serving can exceed safe levels. Toddlers consuming even one small apricot kernel risk being over the safe level.
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Understanding Female HIV Transmission
Glowing virus maps points of entry through entire female reproductive tract for first time.
Genetic Markers Influence Addiction
Differences in vulnerability to cocaine addiction and relapse linked to both inherited traits and epigenetics, U-M researchers find.
Lab-on-a-Chip for Detecting Glucose
By integrating microfluidic chips with fiber optic biosensors, researchers in China are creating ultrasensitive lab-on-a-chip devices to detect glucose levels.
A lncRNA Regulates Repair of DNA Breaks in Breast Cancer Cells
Findings give "new insight" into biology of tough-to-treat breast cancer.
COPD Linked to Increased Bacterial Invasion
Persistent inflammation in COPD may result from a defect in the immune system that allows airway bacteria to invade deeper into the lung.
Detection of HPV in First-Void Urine
Similar sensitivity of HPV test on first void urine sample compared to cervical smear.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!